Antibodies are known to bind their corresponding antigens extremely specifically. If an antibody is directed against a partial amino acid sequence of a protein (an epitope), it is known that this partial sequence can be used alone for its binding.
The specific binding of two biomolecules was compared to the lock and key principle for the first time in the case of enzyme-substrate binding. However, in the 60s Linus Pauling recognized that there was a fundamental difference between enzyme-substrate binding and antibody-antigen binding. The binding site of an enzyme does not completely fit the substrate at all. Rather the binding site of an enzyme appears to be much more similar to the structure of the transition state of a substrate reaction and therefore allows the substrate to have a certain latitude in its structure without the enzyme losing its binding properties for the substrate. In contrast absolute fitting of the antigenic epitope into the binding site of the antibody is required for antigen-antibody binding, which basically excludes any spatial variation of the epitope with regard to antibody binding. It is only by means of this specific epitope/antibody binding that a foreign substance can be specifically eliminated from the organism by an antibody.
Epitopes toward which an antibody is specifically directed are mainly used for two applications. On the one hand, they serve--usually bound to a carrier--as immunogens (vaccines) which cause an organism to produce antibodies which are directed against these epitopes or against antigens which contain these epitopes. On the other hand, such epitopes are used in immunoassays for the specific detection of antibodies in body fluids in which they have been produced by an immune reaction to antigens which contain these epitopes (for example after infection by an infectious organism).
If the epitopes are polypeptides, when they are used in the organism as a vaccine or when they come into contact with body fluids such as serum in diagnostic applications, there is a problem in that the polypeptides are decomposed and lose their function by metabolic degradation, brought about in particular by proteases such as those which occur in body fluids.
It is known that polypeptides which are used for therapeutic purposes, i.e. for binding to enzymes or to hormone receptors in the organism, can be protected from metabolic degradation in the body by modifying the amino acid sequence. A description of such so-called peptide mimetics as therapeutic agents and the production thereof is given inter alia in Giannis, "Angewandte Chemie" 105 (1993) 1303-1326; Lee, Bull Chem. Soc. Jpn 66 (1993) 2006-2010 and Dorsch et al, "Kontakte" (Darmstadt) 1993 (2). However, this modification method did not appear to be applicable to epitopes used for binding antibodies and as immunogens for producing antibodies due to the known high specificity of the epitope-antibody binding.
Recently, at the third European BIAcore Symposium in London 1993, peptide human serum albumin fusion products were proposed for stabilizing such polypeptide epitopes (Integration of Biocore in the Discovery Department S. Reboul et al). However, the coupling of peptide epitopes to human serum albumin merely delays the enzymatic degradation of the polypeptides to a certain extent but does not prevent it.